| ObjectiveWe aimed at observing changes of vital sign from Brain death to cardiac death through establishing gradual onset brain death rabbit models.Methods(1) A total of 15 New Zealand rabbits were randomized to control group(Group A),brain dead 4 hours group(Group B1), brain dead 8 hours group(Group B2),with 5 rabbits in each group. The group A were placed Foley balloon catheter in intracalvarium only; no brain-dead model was established. Brain-dead model was established in group B by increasing intracranial pressure in a modified, slow, and intermittent way. Monitored changes of MAP, HR, RR before pressurize and changes of MAP, HR after stopping salvage. Write down heart living time after stopping salvage.(2) 10 landraces,30 to 40 kg, randomized to experimental group and control group, were used to make 30min cardiac death models through withdrawl life support from brain death model. Place an intravenous cannula through right iliac arteries and veins, connect cannula to ECMO extracorporeal circulation pipes in experimental group. Place the balloon catheter to diaphragm plane through left femoral artery. Start the ECMO to infuse abdominal organs, while adjusting pH and electrolyte. Monitor and record the circulation flow rate, intraperitoneal organ perfusion pressure, venous blood gas, electrolyte, transaminase, bile product, etc. the livers of control group were retrieved after 30min cardiac arrest and stored in cold UW for 4 hrs. Pathological tissue was sliced and stained by HE.(3) ECMO was used to provide support for circulatory or respiratory failure DBD donors and DCD donors. ECMO intervention flow diagrams were established in three China organ donation categories. A retrospective cohort study between circulatory non stable DBD with vasoactive drugs (DBD-drug) and circulatory non stable DBD with ECMO (DBD-ECMO) was made to compare transplant outcome.(4) Establish a clinical randomlized control study protocal to compare the ex vivo preserveation effect between cold storage and normothermica perfusion. After the evaluation of the liver donors and recipients, the informed concent of the operation and joining the clinical trail will be signed. The donated liver will be randomlized to cold storage group or normothermic perfusion group. The liver will be transplanted and the outcome will be analized.Results(1)After intracalvarium pressurize, MAP upgraded(p<0.001); After the progressive intracranial pressure and brain death established, the hemodynamic stability could be maintained during 8h of the brain death state with the management of ventilation and vaso-active medications. The liver and kidney function getting damaged gradually over time. After brain death, cardiac function was not over prolonged recession. MAP, HR gradual declined after the rescue withdrawed.(2) After cardiac arrest 30 min, the liver was obviously congestion appearance of the dark, pathological biopsy showed that hepatic sinus expansion, blood cells clog, erythrocyte aggregation. Circulating blood gas analysis showed severe acidosis. After the ECMO recirculation started, circulation flow rate maintained to 1 L/min, the liver gradually restored bright red, pathological biopsy showed that hepatic sinus expansion disappeared, clogged blood cells dispelled. AST markedly increased to (226.0+28.0) U/L and fell to (150.0+30.0) U/L 4 hr latter. Average bile production was 7.75 mL/h.(3) 21 donors, including 19 DBD,1 DCD and 1 DBCD, have been supported by ECMO. The post-transplant liver PNF incidence was 10%(2/20) in DBD-drug group vs.0 in DBD-ECMO group. Kidney function indicators including creatinine clearance and urine production were significantly better in DBD-ECMO group, as well as decreased kidney DGF rate. Donation success rate increased steadily from 47.8%in 2011 to 84.6%in 2014 after ECMO intervention.(4) Following the clinical trial protocol,20 livers were randomlized into normothermic perfusion group, in which 10 were from DBD donors (DBD-NMP group) and 10 were from DCD donors (DCD-NMP group); 20 livers were randomlized into cold storage group, in which 9 were from DBD donors (DBD-CS group) and 11 were from DCD donors (DCD-CS group). pH levels of DCD-NMP group were significantly lower than those of DBD-NMP group at 15min, lh of normothermic perfusion, which suggested acidosis but gradually increased to 7.30±0.11 at end of the NMP. Glucan levels of the DCD-NMP group were significantly higher than those of DBD-NMP group at 15min, 1h of the normothermic perfion, which gradually decreased to (11.4±5.3)mmol/L at the end of NMP. NMP had prolonged the ex vivo liver preservation duration. AST levels of DCD-NMP group were significantly lower that those of DCD-CS group on 1st,3rd post transplantation DCD-NMP group had signicant shorter hospital stay than DCD-CS group. The discarding rate of DCD-CS group is 45%(4/11), however, that of DCD-NMP group was 10%(1/10).Conclusion(1) When gradual onset brain death rabbit models were established, hemodynamic can be kept steady for relatively long time. Cardiac function didn't deteriorate with prolonging of time after brain dead. MAP and HR were descending gradually after stopping salvage(2) ECMO recirculation in vivo can repair the injured liver from cardiac death for 30 min, decrease transaminase level in perfusate blood and pathologically repair the liver warm ischemia injury.(3) The use of ECMO in assisting circulatory and respiratory function of DBD can reduce liver and kidney injury from vasoactive drugs, thereby improving organ quality and reducing the organ discard rates.(4) Liver normothermic perfusion system provided the new method for ex vivo live function and injury evalution. The levels of pH, glucan, and lactate could assess liver function, which had the advantage of convenient and direct. Liver normothermic perfusion provided a stable physiological environment and could prolong the liver ex vivo preservation duration. The normothermic perfusion had decreased the the incidences of reperfusion syndrome and primary non-function, shorten the ICU stay, decrease the post-transplant AST level and increased the utility of DCD livers, which had important effect on expanding the source of livers. |
PDF Full Text Request